Early Diagnosis of Native and Device-associated Meningitis

Summary

Device-associated meningitis is a severe complication after implantation of various central nervous system (CNS) devices such as ventriculoperitoneal (VP) and ventriculoatrial (VA) shunts, external ventricular drains (EVD), lumbar drains (ELD) and intrathecal pumps. In contrast to native meningitis, these infections are hard to diagnose both clinically and on the laboratory basis due to (i) atypical clinical manifestation, (ii) overlapping inflammation following surgery, and (iii) common culture negativity due to previous antibiotic therapy and slow growth of low-virulent pathogens. Also, device-associated infections are difficult to differentiate from aseptic shunt failure (dysfunction) or "chemical meningitis" caused by underlying neurosurgical condition that prompted the placement of the CNS device (e.g. intracranial hemorrhage).

Both native and device-associated meningitis carry substantial morbidity and mortality. Rapid and reliable diagnosis of meningitis is critical for initiating and choosing optimal treatment and minimizing the brain damage. Since treatment is different in septic than aseptic meningitis, it is paramount to diagnose or exclude septic meningitis as soon as possible.

Several new diagnostic methods, such as cerebrospinal fluid (CSF) procalcitonin, interleukin-6 and polymerase chain reaction (PCR) have been proposed for rapid diagnosis of meningitis. However, insufficient sensitivity and/or specificity, long time until test result, and complexity in handling or interpretation of results limit their use in clinical routine.

In previous studies CSF D-lactate test showed good specificity and sensitivity in patients with native meningitis. This biomarker is pathogen-specific - in contrast to other currently used host-specific biomarkers (leukocyte count, L-lactate, procalcitonin). However, no study on effectiveness of D-lactate test for the diagnosis of device-associated meningitis has been performed.

Successful management of device-associated meningitis depends upon appropriate control of the infectious complications. To deal with such complications, adequate assessment and prediction of the clinical course are needed. Another use of D-lactate test could be his role as prognostic factor of the clinical course of device-associated meningitis.

Conditions

• Bacterial Meningitis
• Fungal Meningitis
• Implant Infection

Interventions

DIAGNOSTIC_TEST

D-lactate test

In device-associated meningitis, CSF will be aspirated before, during or after surgery related to the device, according to the standard practice. Lumbar/ventricular punctures (pre-, intra- and/or postoperatively) and external ventricular (EVD) and lumbar drainage (ELD) aspiration will be performed by neurologist or neurosurgeon according to standardized aseptic techniques. In patients with native meningitis, CSF will be aspirated by lumbar puncture, according the standard practice. The D-lactate test will be performed using spectrophotometric enzyme assay according to the manufacturer's instructions (D-Lactate Colorimetric Assay).

DIAGNOSTIC_TEST

Standard diagnostic tests

In device-associated meningitis, CSF will be aspirated before, during or after surgery related to the device, according to the standard practice. Lumbar/ventricular punctures (pre-, intra- and/or postoperatively) and external ventricular (EVD) and lumbar drainage (ELD) aspiration will be performed by neurologist or neurosurgeon according to standardized aseptic techniques. In patients with native meningitis, CSF will be aspirated by lumbar puncture, according the standard practice. The standard diagnostic tests will be performed according to standard diagnostic laboratory instructions.

Sponsors & Collaborators

• Charite University, Berlin, Germany

  lead OTHER

Principal Investigators

• Andrej Trampuz, PD Dr. med · Charite University, Berlin, Germany

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-01

Primary Completion

2024-05-31

Completion

2024-05-31

Countries

• Germany

Study Locations